Research Topics
Genomes and Genes
| Moosa MohammadiSummaryAffiliation: New York University Country: USA Publications
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Publications
Structural basis for fibroblast growth factor receptor activationMoosa Mohammadi
Department of Pharmacology, New York University School of Medicine, 550 First Avenue, MSB 425, New York, NY 10016, USA
Cytokine Growth Factor Rev 16:107-37. 2005....- A protein canyon in the FGF-FGF receptor dimer selects from an à la carte menu of heparan sulfate motifsMoosa Mohammadi
Department of Pharmacology, New York University School of Medicine, New York, NY 10016, USA
Curr Opin Struct Biol 15:506-16. 2005.... 
Analysis of mutations in fibroblast growth factor (FGF) and a pathogenic mutation in FGF receptor (FGFR) provides direct evidence for the symmetric two-end model for FGFR dimerizationOmar A Ibrahimi
Department of Pharmacology, New York University School of Medicine, New York, NY 10016, USA
Mol Cell Biol 25:671-84. 2005..Taken together, the data validate the symmetric two-end model of FGFR dimerization and argue against the asymmetric model of FGFR dimerization...- Structural basis by which alternative splicing modulates the organizer activity of FGF8 in the brainShaun K Olsen
Department of Pharmacology, New York University School of Medicine, New York, New York 10016, USA
Genes Dev 20:185-98. 2006..Consistent with the indispensable role of FGF8 in embryonic development, we show that the FGF8 mode of receptor binding appeared as early as in nematodes and has been preserved throughout evolution... - Fibroblast growth factor (FGF) homologous factors share structural but not functional homology with FGFsShaun K Olsen
Department of Pharmacology, New York University School of Medicine, New York, New York 10016, USA
J Biol Chem 278:34226-36. 2003..Hence, FHFs and FGFs bear striking structural similarity but have diverged to direct related surfaces toward interaction with distinct protein targets... - Insights into the molecular basis for fibroblast growth factor receptor autoinhibition and ligand-binding promiscuityShaun K Olsen
Departments of Pharmacology and Microbiology, New York University School of Medicine, New York, NY 10016, USA
Proc Natl Acad Sci U S A 101:935-40. 2004..Importantly, comparison of the three FGF1-FGFR structures shows that the flexibility of the betaC'-betaE loop is a major determinant of ligand-binding specificity and promiscuity... - Understanding the molecular basis of Apert syndromeOmar A Ibrahimi
Department of Pharmacology and the Institute of Reconstructive Plastic Surgery, New York University School of Medicine, New York, NY 10016, USA
Plast Reconstr Surg 115:264-70. 2005..In this review, the authors provide the clinician with a basic overview of these findings and their therapeutic implications... - Molecular insights into the klotho-dependent, endocrine mode of action of fibroblast growth factor 19 subfamily membersRegina Goetz
Department of Pharmacology, New York University School of Medicine, New York, NY 10016, USA
Mol Cell Biol 27:3417-28. 2007..Klotho/betaKlotho have evolved as a compensatory mechanism for the poor ability of heparin/heparan sulfate to promote binding of FGF19, -21, and -23 to their cognate receptors... - Crystal structure of a fibroblast growth factor homologous factor (FHF) defines a conserved surface on FHFs for binding and modulation of voltage-gated sodium channelsRegina Goetz
Department of Pharmacology, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA
J Biol Chem 284:17883-96. 2009..The mutations also disabled FHF modulation of voltage-dependent fast inactivation of sodium channels in neuronal cells. Based on our data, we propose that FHFs constitute auxiliary subunits for Navs... - A crystallographic snapshot of tyrosine trans-phosphorylation in actionHuaibin Chen
Department of Pharmacology and Kimmel Center for Biology and Medicine at Skirball Institute, New York University School of Medicine, New York, NY 10016, USA
Proc Natl Acad Sci U S A 105:19660-5. 2008..We propose that the salient mechanistic features of Y769 trans-phosphorylation are applicable to trans-phosphorylation of the equivalent major phosphorylation sites in many other RTKs... - Conversion of a paracrine fibroblast growth factor into an endocrine fibroblast growth factorRegina Goetz
Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York 10016, USA
J Biol Chem 287:29134-46. 2012.... - The alternatively spliced acid box region plays a key role in FGF receptor autoinhibitionJuliya Kalinina
Department of Pharmacology, New York University School of Medicine, 550, First Avenue, New York, NY 10016, USA
Structure 20:77-88. 2012..These data, together with the strong amino acid sequence conservation of the AB subregion among FGFR orthologs, highlight the universal role of the AB subregion in FGFR autoinhibition... - Plasticity in interactions of fibroblast growth factor 1 (FGF1) N terminus with FGF receptors underlies promiscuity of FGF1Andrew Beenken
Department of Pharmacology, New York University School of Medicine, New York, New York 10016, USA
J Biol Chem 287:3067-78. 2012.... - Kinetic model for FGF, FGFR, and proteoglycan signal transduction complex assemblyOmar A Ibrahimi
Department of Pharmacology, New York University School of Medicine, New York, New York 10016, USA
Biochemistry 43:4724-30. 2004..In contrast, alternative models for the kinetic assembly of a ternary complex in which binary FGF-FGFR or FGFR-HSPG complexes are intermediates do not conform well with the experimental data... - Proline to arginine mutations in FGF receptors 1 and 3 result in Pfeiffer and Muenke craniosynostosis syndromes through enhancement of FGF binding affinityOmar A Ibrahimi
Department of Pharmacology, New York University School of Medicine, New York, NY 10016, USA
Hum Mol Genet 13:69-78. 2004.... - Homodimerization controls the fibroblast growth factor 9 subfamily's receptor binding and heparan sulfate-dependent diffusion in the extracellular matrixJuliya Kalinina
Department of Pharmacology of New York University School of Medicine, New York, New York 10016, USA
Mol Cell Biol 29:4663-78. 2009.... - Biochemical analysis of pathogenic ligand-dependent FGFR2 mutations suggests distinct pathophysiological mechanisms for craniofacial and limb abnormalitiesOmar A Ibrahimi
Department of Pharmacology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA
Hum Mol Genet 13:2313-24. 2004..We suggest that elevated AS mutant FGFR2b signaling may account for the dermatological manifestations of AS... - Structural basis by which alternative splicing confers specificity in fibroblast growth factor receptorsBrian K Yeh
Department of Pharmacology, New York University School of Medicine, New York, NY 10016, USA
Proc Natl Acad Sci U S A 100:2266-71. 2003..We propose that ligand-induced conformational change in FGFRs may also play an important role in determining specificity for other FGF-FGFR complexes... - A molecular brake in the kinase hinge region regulates the activity of receptor tyrosine kinasesHuaibin Chen
Department of Pharmacology, New York University School of Medicine, New York, NY 10016, USA
Mol Cell 27:717-30. 2007..Pathogenic mutations activate FGFRs and other RTKs by disengaging the brake either directly or indirectly... - Isolated C-terminal tail of FGF23 alleviates hypophosphatemia by inhibiting FGF23-FGFR-Klotho complex formationRegina Goetz
Department of Pharmacology, New York University School of Medicine, New York, NY 10016, USA
Proc Natl Acad Sci U S A 107:407-12. 2010..We propose that peptides derived from the C-terminal tail of FGF23 or peptidomimetics and small-molecule organomimetics of the C-terminal tail can be used as therapeutics to treat renal phosphate wasting... - Klotho coreceptors inhibit signaling by paracrine fibroblast growth factor 8 subfamily ligandsRegina Goetz
Department of Pharmacology, New York University School of Medicine, New York, New York, USA
Mol Cell Biol 32:1944-54. 2012..Based on this binding site overlap, we conclude that while Klotho coreceptors enhance binding affinity of FGFR for endocrine FGFs, they actively suppress binding of FGF8 subfamily ligands to FGFR... 
The FGF family: biology, pathophysiology and therapyAndrew Beenken
Department of Pharmacology, New York University School of Medicine, New York, New York 10016, USA
Nat Rev Drug Discov 8:235-53. 2009....- Fibroblast growth factor 21 promotes bone loss by potentiating the effects of peroxisome proliferator-activated receptor γWei Wei
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Proc Natl Acad Sci U S A 109:3143-8. 2012..Therefore, FGF21 is a critical rheostat for bone turnover and a key integrator of bone and energy metabolism. These results reveal that skeletal fragility may be an undesirable consequence of chronic FGF21 administration... - The structural biology of the FGF19 subfamilyAndrew Beenken
Department of Pharmacology, New York University School of Medicine, New York, NY, USA
Adv Exp Med Biol 728:1-24. 2012..The isolated FGF23 C-terminus can be used to effectively inhibit the formation of the FGF23-FGFR1c-αklotho complex and alleviate hypophosphatemia in renal phosphate disorders due to elevated levels of FGF23... - Pregnane X receptor activation induces FGF19-dependent tumor aggressiveness in humans and miceHongwei Wang
Albert Einstein Cancer Center, Albert Einstein College of Medicine, New York, New York 10461, USA
J Clin Invest 121:3220-32. 2011..Taken together, these data indicate that colon cancer growth in the presence of a specific PXR ligand results from tumor-specific induction of FGF19. These observations may lead to improved therapeutic regimens for colon carcinomas... - Structural basis for activation of fibroblast growth factor signaling by sucrose octasulfateBrian K Yeh
Departments of Pharmacology Medicine, New York University School of Medicine, New York, New York 10016, USA
Mol Cell Biol 22:7184-92. 2002..Moreover, the FGF-FGFR-SOS structure provides an attractive template for the development of easily synthesized SOS-related heparin agonists and antagonists that may hold therapeutic potential... - FGF21 induces PGC-1alpha and regulates carbohydrate and fatty acid metabolism during the adaptive starvation responseMatthew J Potthoff
Department of Pharmacology, Howard Hughes Medical Institute, Advanced Imaging Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Proc Natl Acad Sci U S A 106:10853-8. 2009..These results reveal an unexpected relationship between FGF21 and PGC-1alpha and demonstrate an important role for FGF21 in coordinately regulating carbohydrate and fatty acid metabolism during the progression from fasting to starvation... - Urothelial tumor initiation requires deregulation of multiple signaling pathways: implications in target-based therapiesHaiping Zhou
Department of Urology, NYU Cancer Institute, New York University School of Medicine, New York, NY 10016, USA
Carcinogenesis 33:770-80. 2012.... - Hedgehogs like it sweet, tooAndrew Beenken
Department of Pharmacology, New York University School of Medicine, New York, NY 10016, USA
Proc Natl Acad Sci U S A 103:17069-70. 2006 - Structure-based mutational analyses in FGF7 identify new residues involved in specific interaction with FGFR2IIIbIfat Sher
Department of Biology, Technion Israel Institute of Technology, 32000 Haifa, Israel
FEBS Lett 552:150-4. 2003..Altogether, these results provide the basis for understanding how receptor-binding specificity of FGF7 is conferred at the structural level... - Analysis of the biochemical mechanisms for the endocrine actions of fibroblast growth factor-23Xijie Yu
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
Endocrinology 146:4647-56. 2005..Our biochemical findings provide important insights into the molecular mechanisms by which dysregulated FGF23 signaling leads to disorders of hyper- and hypophosphatemia... - A homozygous missense mutation in human KLOTHO causes severe tumoral calcinosisShoji Ichikawa
Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202 5121, USA
J Clin Invest 117:2684-91. 2007.... - Receptor specificity of the fibroblast growth factor family. The complete mammalian FGF familyXiuqin Zhang
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, Missouri 63110, USA
J Biol Chem 281:15694-700. 2006..This study completes the mitogenesis-based comparison of receptor specificity of the entire FGF family under standard conditions and should help in interpreting and predicting in vivo biological activity... - Mutations in fibroblast growth factor receptor 1 cause both Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadismNelly Pitteloud
Reproductive Endocrine Unit of the Department of Medicine and Harvard Reproductive Endocrine Science Centers, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA
Proc Natl Acad Sci U S A 103:6281-6. 2006..These mutations also account for some of the mixed pedigrees, thus challenging the current idea that KS and nIHH are distinct entities... - Impaired FGF signaling contributes to cleft lip and palateBridget M Riley
Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA
Proc Natl Acad Sci U S A 104:4512-7. 2007..The data suggest that the FGF signaling pathway may contribute to as much as 3-5% of NS CLP and will be a consideration in the clinical management of CLP... - BetaKlotho is required for metabolic activity of fibroblast growth factor 21Yasushi Ogawa
Department of Pathology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA
Proc Natl Acad Sci U S A 104:7432-7. 2007..Importantly, administration of FGF21 into mice induces MAP kinase phosphorylation in white adipose tissue and not in tissues without betaKlotho expression. Thus, betaKlotho functions as a cofactor essential for FGF21 activity... - Tissue-specific expression of betaKlotho and fibroblast growth factor (FGF) receptor isoforms determines metabolic activity of FGF19 and FGF21Hiroshi Kurosu
Departments of Pathology and Molecular Biology, University of Texas Southwestern Medical Center at Dallas, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA
J Biol Chem 282:26687-95. 2007..We conclude that the expression of betaKlotho, in combination with particular FGFR isoforms, determines the tissue-specific metabolic activities of FGF19 and FGF21... - Endocrine regulation of the fasting response by PPARalpha-mediated induction of fibroblast growth factor 21Takeshi Inagaki
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Cell Metab 5:415-25. 2007..These findings demonstrate an unexpected role for the PPARalpha-FGF21 endocrine signaling pathway in regulating diverse metabolic and behavioral aspects of the adaptive response to starvation... - The parathyroid is a target organ for FGF23 in ratsIddo Z Ben-Dov
Minerva Center for Calcium and Bone Metabolism, Nephrology Services, Hadassah Hebrew University Medical Center, Jerusalem, Israel
J Clin Invest 117:4003-8. 2007..These data indicate that FGF23 acts directly on the parathyroid through the MAPK pathway to decrease serum PTH. This bone-parathyroid endocrine axis adds a new dimension to the understanding of mineral homeostasis... - Somatic FGF9 mutations in colorectal and endometrial carcinomas associated with membranous beta-cateninWael M Abdel-Rahman
Department of Medical Genetics, University of Helsinki, Helsinki, Finland
Hum Mutat 29:390-7. 2008..These data suggest that FGF9 plays a role in colorectal and endometrial carcinogenesis... - Inhibition of growth hormone signaling by the fasting-induced hormone FGF21Takeshi Inagaki
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Cell Metab 8:77-83. 2008..Chronic exposure to FGF21 markedly inhibits growth in mice. These data suggest a central role for FGF21 in inhibiting growth as part of its broader role in inducing the adaptive response to starvation... - FGF-23-Klotho signaling stimulates proliferation and prevents vitamin D-induced apoptosisDamian Medici
Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115, USA
J Cell Biol 182:459-65. 2008..These data provide new insights into the physiological roles of FGF-23 and Klotho...
Research Grants
- MECHANISMS OF FGF RECEPTOR REGULATION AND SIGNALINGMoosa Mohammadi; Fiscal Year: 2009..Thus the results of our studies should facilitate the development of novel therapeutics for the treatment of a variety of human diseases. ..
- MECHANISMS OF FGF RECEPTOR REGULATION AND SIGNALINGMoosa Mohammadi; Fiscal Year: 2004..that the results of these structural and functional analyses will facilitate the rational design of novel FGF antagonists for the treatment of cancer as well as enhance our understanding of other heparin-binding growth factors ..
- MECHANISMS OF FGF RECEPTOR REGULATION AND SIGNALINGMoosa Mohammadi; Fiscal Year: 2009..abstract_text> ..